Suppression of Humoral Immune Responses by Dialkylnitrosamines: Structure-Activity Relationships

Suppression of Humoral Immune Responses by Dialkylnitrosamines:Structure-Activity Relationships. KAMINSKI, N. E., JORDAN, S.D., PAGE, D., KIM, B. S., AND HOLSAPPLE, M. P. (1989). Fundam.Appl Toxicol 12,321-332. Comparisons between chemical structureof N, N-dialkylnitrosamine congeners and their ability to alterthe Day 4 IgM antibody response to sRBC, body weights. and organweights of female B6C3F1 mice were investigated. Short-chainnitrosamine congeners were selected for these studies on thebasis of two criteria: (1) congeners wth symmetrical aliphaticchain length [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine(DEN), N-nitrdipropylamine (DPN), N-nitrosodibutylamine (DBN)]and (2) congeners possessing an N-methyl group [N-nitrosomethylethylamine(MEN), N-nitrosomethylpropylamine (MPN), and N-nitrosomethylbutylamine(MBN)]. The immunotoxicity of each congener was evaluated basedon the compound's ability to suppress the in vivo sRBC antibodyresponse following 7 consecutive days of treatment. An ED50dose was calculated, using a linear regression analysis, foreach congener and represents the millimoles of congener perkilogram body weight required to cause a 50% suppression ofthe sRBC response. These studies demonstrated two general trends:(1) those dialkylnitrosamine congeners that possessed an N-methylgroup were most immunotoxic and exhibited comparable ED50 concentrations(42-183 µmol/kg); and (2) dialkylnitrosamine congenerspossessing symmetrical aliphatic chains demonstrated an inverserelationship between aliphatic chain length and immunotoxicpotency—DMN (62 µmol/kg) > DEN (276 µmol/kg)> DPN (467 µmol/kg) > DMN (1557 µmol/kg).Comparisons were also made between the immunotoxic potency ofvarious nitrosamine congeners in the whole animal and theirpotency in an in vitro hepatocyte-spleen cell coculture system.     

Effects on Fertility of Rabbits After Active Immunization With Rat Testicular Cytochrome ct

ABSTRACT: A Male rabbit was immunized with rat testicular cytochrome (Cyt) c_t and mated with normal, unimmunized females. The matings resulted in abnormal pregnancies: no offspring or stillborn or undersized liveborn offspring weighing 25–30 gm each. Another unusual observation was that fur-pulling behavior, normally exhibited by pregnant female rabbits at the end of the gestational period, was absent in all of these pregnancies. Therefore, immunization of a normal rabbit with testicular cyt c_t appeared to interfere with physiological and behavioral aspects of pregnancy in normal female rabbits. The immunological basis of these findings remains to be determined.     

Effects of long working hours and the night shift on severe sleepiness among workers with 12‐hour shift systems for 5 to 7 consecutive days in the automobile factories of Korea

We investigated the effects of 12‐hour shift work for five to seven consecutive days and overtime on the prevalence of severe sleepiness in the automobile industry in Korea. [Correction added after online publication 28 Nov: Opening sentence of the summary has been rephrased for better clarity.] A total of 288 randomly selected male workers from two automobile factories were selected and investigated using questionnaires and sleep‐wake diaries in South Korea. The prevalence of severe sleepiness at work [i.e. Karolinska Sleepiness Scale (KSS) score of 7 or higher] was modeled using marginal logistic regression and included theoretical risk factors related to working hours and potential confounding factors related to socio‐economic status, work demands, and health behaviors. Factors related to working hours increased the risk for severe sleepiness at the end of the shift in the following order: the night shift [odds ratio (OR): 4.7; 95% confidence interval (CI): 3.6–6.0)], daily overtime (OR: 2.2; 95% CI: 1.7–2.9), weekly overtime (OR: 1.6; 95% CI: 1.0–2.6), and night overtime (OR: 1.6; 95% CI: 0.8–3.0). Long working hours and shift work had a significant interactive effect for severe sleepiness at work. Night shift workers who worked for 12 h or more a day were exposed to a risk of severe sleepiness that was 7.5 times greater than day shift workers who worked less than 11 h. Night shifts and long working hours were the main risk factors for severe sleepiness among automobile factory workers in Korea. Night shifts and long working hours have a high degree of interactive effects resulting in severe sleepiness at work, which highlight the need for immediate measures to address these characteristics among South Korean labor force patterns.     

HLA-DR4 SUBTYPE AND -B ALLELES IN DQB1*0302-POSITIVE HAPLOTYPES ASSOCIATED WITH IDDM

We determined the distribution of DR4 subtypes in 309 DQB1*0302-positive haplotypes found in insulin-dependent diabetes mellitus (IDDM) patients and 70 control haplotypes present only in healthy family members. An increased frequency of DRB1*0401 allele (74.4% vs. 55.7%, P = 0.003) and a decrease of DRB1*0404 allele (23.6% vs. 40.0%, P = 0.0064) was revealed. A further analysis of extended haplotypes demonstrated strong linkages between various B alleles and DRB1*04 subtypes. HLA-B39 was more frequent in DRB1*0404–DQB1*0302-positive IDDM haplotypes compared with control ones (37.0% vs. 14.3%, P = 0.049), suggesting an involvement of the region telomeric to HLA-DRB1 in the susceptibility to IDDM.     

子宫颈癌△Np63蛋白表达的临床病理学意义

目的探讨△Np63蛋白表达在子宫颈癌不同组织学类型中的临床病理学意义。方法43例子宫颈上皮内瘤变(cervi-calintraepithelialneoplasia,CIN)(包括15例CIN1,6例CIN2和22例CIN3),21例角化型和33例大细胞非角化型宫颈鳞状细胞癌(鳞癌)、40例腺癌、4例神经内分泌癌、4例腺鳞癌、2例移行细胞癌、2例玻璃样细胞癌和1例腺瘤样基底细胞癌的标本选自韩国高丽大学安岩附属医院和延边妇幼保健医院病理科,应用免疫组化染色方法检测△Np63蛋白在上述病变组织中的表达情况。结果△Np63蛋白在所有子宫颈鳞癌标本中呈阳性表达,而在所有腺癌则为阴性。随着CIN病变级别的增加,△Np63蛋白表达的分布范围也逐渐增多,而且在不同组织学类型的子宫颈癌中,合并鳞状细胞分化(associatedwithsquamousdifferentiationofuterinecervix)的病变区△Np63表达增强,但在腺性分化和神经内分泌分化的区域△Np63则不表达。结论△Np63蛋白检测对区分子宫颈癌组织学类型的具有重要意义,且对子宫颈腺癌的鉴别诊断是一个非常有用的指标。     

砂仁提取物对实验性糖尿病大鼠的降血糖作用

[目的]探讨砂仁提取物对实验性糖尿病大鼠的降血糖作用.[方法]利用链脲佐菌素制作大鼠糖尿病动物模型,给糖尿病治疗组大鼠腹腔注射砂仁提取物20 mg每日2次,共2周,观察治疗前后血糖的变化及胰岛β细胞超微结构变化.[结果]糖尿病治疗组大鼠血糖明显降低,与糖尿病对照组比较有显著性差异;砂仁提取物对糖尿病大鼠胰岛β细胞具有明显的保护作用,并可改善胰岛β细胞超微结构变化.[结论]砂仁提取物对实验性糖尿病大鼠具有降血糖作用.     

电脉冲介导基因转移效率的实验研究

目的　研究电脉冲介导的基因转移效率及其最佳的基因转移的电脉冲参数。方法　用微量注射器将pcD2/LacZ质粒10μg,在昆明小鼠的股四头肌注射,1～2min内在注射部位给予不同参数的电脉冲刺激(不同的电脉冲参数每组10只小鼠),然后进行β-半乳糖苷酶活性的测定或酶组织化学染色。同时设空白对照组及单纯注射组。结果　电脉冲可明显增加LacZ基因的表达,电脉冲组的β-半乳糖苷酶活性（131.6U/mg±86.5U/mg蛋白）是单纯注射组（4.9U/mg±1.0U/mg蛋白）的30倍（P<0.05）。组织化学染色结果表明电脉冲组肌肉组织中β-半乳糖苷酶蓝色颗粒的数目和染色的程度均明显高于单纯肌肉注射组。当电脉冲参数电压200V/cm,波宽40ms,脉冲次数6次和频率1Hz时,可获得最高的基因表达效率。结论　在最佳的电脉冲参数条件下,电脉冲介导的基因转移可获得较高的基因表达。